Linked Life Data

10946260

Source:http://linkedlifedata.com/resource/pubmed/id/10946260

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-9-19
pubmed:abstractText
The immunosuppressive drug, mycophenolate mofetil (MMF), has been successfully introduced in allogeneic transplantation medicine and, more recently, in the treatment of autoimmune skin disorders. MMF inhibits lymphocyte proliferation via a blockade of the enzyme inosine 5'-monophosphate dehydrogenase, an enzyme on which lymphocytes solely depend to generate the purines necessary for DNA/RNA synthesis. To investigate the effects of MMF on cutaneous immune responses, a murine model of contact hypersensitivity (CHS) was used, with oxazolone or trinitrochlorobenzene as a contact allergen. Compared with the respective vehicle, i.p. applied MMF significantly inhibited the elicitation and, surprisingly, the induction of CHS responses. This prompted further studies into the effects of MMF on Ag presentation. Bone marrow-derived dendritic cells (DC) were cultured with GM-CSF and IL-4 in the presence of MMF and were tested for their Ag-presenting capacity. Sensitization and elicitation of CHS and delayed-type hypersensitivity responses by s. c. injected haptenated DC were reduced upon preincubation of DC with MMF. CHS responses were not impaired upon resensitization, indicating that MMF does not induce hapten-specific immunotolerance. In addition, MMF decreased the ability of DC to stimulate allogeneic T cells in MLR assays. Accordingly, flow cytometric analyses revealed a dose-dependent reduction of the expression of CD40, CD80, CD86, I-A, and ICAM-1 on DC with a concurrent reduction of IL-12 production. These data suggest that MMF, in addition to affecting T lymphocytes, directly affects APC, resulting in an impairment of immune responses. They furthermore point to a possible role of inosine 5'-monophosphate dehydrogenase in the maturation of DC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
165
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2374-81
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10946260-Animals, pubmed-meshheading:10946260-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:10946260-Cell Count, pubmed-meshheading:10946260-Cell Differentiation, pubmed-meshheading:10946260-Cells, Cultured, pubmed-meshheading:10946260-Dendritic Cells, pubmed-meshheading:10946260-Dermatitis, Contact, pubmed-meshheading:10946260-Epidermis, pubmed-meshheading:10946260-Female, pubmed-meshheading:10946260-Haptens, pubmed-meshheading:10946260-Hypersensitivity, Delayed, pubmed-meshheading:10946260-Immune Tolerance, pubmed-meshheading:10946260-Immunosuppressive Agents, pubmed-meshheading:10946260-Injections, Subcutaneous, pubmed-meshheading:10946260-Interleukin-12, pubmed-meshheading:10946260-Langerhans Cells, pubmed-meshheading:10946260-Lipopolysaccharides, pubmed-meshheading:10946260-Lymphocyte Activation, pubmed-meshheading:10946260-Mice, pubmed-meshheading:10946260-Mice, Inbred BALB C, pubmed-meshheading:10946260-Mice, Inbred C57BL, pubmed-meshheading:10946260-Mycophenolic Acid
pubmed:year
2000
pubmed:articleTitle
Mycophenolate mofetil impairs the maturation and function of murine dendritic cells.
pubmed:affiliation
Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, Department of Dermatology, University of Münster, Münster, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't